ArticleHepatology international2024
The upregulation of Annexin A2 by TLR4 pathway facilitates lipid accumulation and liver injury via blocking AMPK/mTOR-mediated autophagy flux during the development of non-alcoholic fatty liver disease.
Article in Hepatology international, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Inappropriate Diet Exacerbates Metabolic Dysfunction-Associated Steatotic Liver Disease via Abdominal Obesity.Nutrients · 2024Pooled it
- Persistent ZnAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- [The role of hepatocyte programmed cell death in liver fibrosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Lipophagy in disease: signaling control, organelle communication, and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Annexin A2 Is Associated with Dietary Cholesterol-Induced Metabolic Dysregulation and the Progression of Hepatic Fibrosis.Metabolites · 2026Article
- The Extracellular Matrix in Liver Regeneration: Biological and Therapeutic Insights.Bioengineering (Basel, Switzerland) · 2026Review
- TM9SF1 Aggravates Liver Ischemia-Reperfusion Injury by Promoting Autophagy.Inflammation · 2026Article
- Dysregulation of the AMPK-SREBP1-FASN axis in MASLD: driving a vicious cycle of lipotoxicity and metabolic-immune crosstalk.Lipids in health and disease · 2026Review
- ANXA2 in hepatocellular carcinoma: orchestrating tumorigenesis, progression, and therapeutic resistance toward precision targeting.Journal of translational medicine · 2025Review
- Comprehensive identification of crucial biomarkers and therapeutic targets in cholestasis via integrated single-cell RNA and transcriptome sequencing analysis.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Targeting Lipophagy in Liver Diseases: Impact on Oxidative Stress and Steatohepatitis.Antioxidants (Basel, Switzerland) · 2025Review
- [Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Gut microbiota heterogeneity in non-alcoholic fatty liver disease: a narrative review of drivers, mechanisms, and clinical relevance.Frontiers in microbiology · 2025Review
- Role of the Annexin A protein family in liver diseases: insights and therapeutic opportunities.Frontiers in pharmacology · 2025Review
- High levels of serum hypersensitive C-reactive protein are associated with non-alcoholic fatty liver disease in non-obese people: a cross-sectional study.European journal of medical research · 2024Article
- Oxidative Stress and Annexin A2 Differential Expression in Free Fatty Acids-Induced Non-Alcoholic Fatty Liver Disease in HepG2 Cells.International journal of molecular sciences · 2024Article
- Hypoxia-Preconditioned BMSC-Derived Exosomes Induce Mitophagy via the BNIP3-ANAX2 Axis to Alleviate Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Bibliometric analysis of lipophagy:2013 to 2023.Heliyon · 2024Review
- Autophagy and inflammation an intricate affair in the management of obesity and metabolic disorders: evidence for novel pharmacological strategies?Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsNon-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. In this study, we aimed to investigate the role and regulatory mechanism of Annexin A2 (ANXA2) in the pathogenesis of NAFLD.
methodsHistological analyses and ELISA were used to illuminate the expression of ANXA2 in NAFLD and healthy subjects. The role of ANXA2 was evaluated using high-fat diet (HFD)-fed mice via vein injection of adeno-associated viruses (AAV) knocking down ANXA2 or non-targeting control (NC) shRNAs. Moreover, HepG2 and LO2 cells were employed as in vitro hepatocyte models to investigate the expression and function of ANXA2.
resultsANXA2 was confirmed to be one of three hub genes in liver injury, and its expression was positively correlated with NAFLD activity score (NAS) and macrophage infiltration in NAFLD. Moreover, ANXA2 was significantly upregulated in NAFLD patients and HFD-fed mice. LPS/TLR4 pathway strongly upregulated ANXA2 expression, which is mediated by direct ANXA2 promoter binding by TLR4 downstream NF-κB p65 and c-Jun transcription factors. Increased ANXA2 expression was correlated with decreased autophagy flux and autophagy was activated by the depletion of ANXA2 in the models of NAFLD. Furthermore, ANXA2 interference led to the activation of AMPK/mTOR signaling axis, which may play a causal role in autophagy flux and the amelioration of steatosis.
conclusionsANXA2 is a pathological predictor and promising therapeutic target for NAFLD. ANXA2 plays a crucial role in linking inflammation to hepatic metabolic disorder and injury, mainly through the blockage of AMPK/mTOR-mediated lipophagy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.